Type 2 Diabetes

Screening and Treatment Guideline

Prevention ..................................................................................................................................................... 2 Screening Recommendations and Tests ...................................................................................................... 2 Diagnosis....................................................................................................................................................... 2 Treatment ...................................................................................................................................................... 4 Goals ......................................................................................................................................................... 4 Lifestyle modifications and non-pharmacologic options ............................................................................ 4 Blood glucose controlpharmacologic options ........................................................................................ 5 ASCVD prevention .................................................................................................................................... 7 Comorbidity treatment ............................................................................................................................... 7 Follow-up/Monitoring ..................................................................................................................................... 8 Periodic monitoring of conditions and complications ................................................................................ 8 Medication monitoring ............................................................................................................................. 10 Recommended comorbidity screening .................................................................................................... 10 Recommended immunizations ................................................................................................................ 10 Evidence Summary ..................................................................................................................................... 11 References .................................................................................................................................................. 15 Guideline Development Process and Team ............................................................................................... 17 Appendix 1. Recommendation Grade Labels ............................................................................................. 18

Last guideline approval: May 2012

Guidelines are systematically developed statements to assist patients and providers in choosing appropriate health care for specific clinical conditions. While guidelines are useful aids to assist providers in determining appropriate practices for many patients with specific clinical problems or prevention issues, guidelines are not meant to replace the clinical judgment of the individual provider or establish a standard of care. The recommendations contained in the guidelines may not be appropriate for use in all circumstances. The inclusion of a recommendation in a guideline does not imply coverage. A decision to adopt any particular recommendation must be made by the provider in light of the circumstances presented by the individual patient.

Type 2 Diabetes Screening and Treatment Guideline Copyright 19962013 Group Health Cooperative. All rights reserved.

Prevention
Studies have shown that increasing physical activity and eating a healthy diet can significantly delay the onset of type 2 diabetes, including for patients diagnosed with impaired glucose tolerance. Studies have also shown the use of metformin can delay the diagnosis of diabetes for patients with impaired glucose intolerance, but there is no evidence that either metformin or valsartan leads to long-term better clinical outcomes for patients.

Screening Recommendations and Tests

Table 1. Recommendations for screening for diabetes Population eligible for screening Men and nonpregnant women with hypertension
Grade B

Test(s) Fasting plasma glucose or HbA1c Fasting plasma glucose or HbA1c HbA1c HbA1c 2-hour glucose tolerance

Frequency Every 2 years1

Men and nonpregnant women with impaired fasting glucose Expert opinion Nonpregnant women with a history of gestational diabetes Pregnant women (See the Group Health Gestational Diabetes Guideline)
1

Annually

Annually Screen at initial prenatal care visit Screen at 2428 weeks

The available evidence does not suggest an ideal screening frequency. Group Health recommends screening of adults with hypertension every 2 years.

The American Diabetes Association recommends screening patients who are overweight or obese (BMI of 25 or higher) and who have additional risk factors for diabetes (Table 4 on page S1 4), such as highrisk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander); family history of one or more first-degree relatives with type 2 diabetes; or history of polycystic ovarian disease. The U.S. Preventive Services Task Force does not make the same recommendation, but it is reasonable to have a higher clinical index of suspicion for type 2 diabetes among adults with multiple risk factors and to use clinical judgment or shared decision making about whether to screen.

Diagnosis
Diagnosis for an asymptomatic patient requires 2 abnormal test results, which can be from the same test on different days, or from different tests on the same day or on different days. If only one comes back abnormal, then repeat the abnormal test on a different day. If it comes back abnormal again, then you have the diagnosis of diabetes. Diagnosis for a patient with classic symptoms of hyperglycemia (i.e., polyuria, polydipsia, weight loss) can be made with a single random plasma glucose result of 200 mg/dL or higher. A repeat measurement is not needed.

Type 2 Diabetes Screening and Treatment Guideline

Table 2. Recommendations for diagnosing diabetes Test HbA1c Results 6.5% or higher 5.76.4% Lower than 5.7% Random plasma glucose 200 mg/dL or higher 140199 mg/dL Lower than 140 mg/dL Fasting plasma glucose 126 mg/dL or higher 100125 mg/dL Lower than 100 mg/dL
1

Interpretation Diabetes Impaired glucose tolerance1 Normal Diabetes Impaired glucose tolerance1 Normal Diabetes Impaired glucose tolerance1 Normal

Impaired glucose tolerance (IGT) is similar to impaired fasting glucose (IFG) but is diagnosed with a confirmed oral glucose tolerance test (OGTT). Both IGT and IFG are risk factors for future diabetes and for cardiovascular disease. They are sometimes jointly referred to as pre-diabetes. Group Health recommends avoiding the term pre-diabetes because not all patients with IGT and/or IFG will develop diabetes.

Patients with type 2 diabetes most commonly present as overweight, hyperglycemic, and nonketotic, with gradual onset of symptoms such as fatigue, blurred vision, polydipsia, and polyuria. Consider islet cell antibody (ICA) with reflex to glutamic acid decarboxylase antibody (GADA) testing for the following patient populations: Children and teenagers to distinguish early type 1 diabetes from type 2 diabetes. Older adults who are not overweight who are not responding well to oral hypoglycemic and lifestyle (diet/exercise) modification. The following laboratory tests are not recommended: Fasting C-peptide is not recommended because the test cannot distinguish well between people without diabetes and those with impaired endogenous insulin secretion. C-peptide is released from a person's pancreas in equimolar amounts to endogenous insulin. Because the amount of endogenous insulin secreted is dependent on a patient's blood glucose level, low or undetectable C-peptide levels may indicate either an inability to produce insulin or an absence of insulin secretion due to low blood sugar levels. In the latter case, a person without diabetes would not secrete much C-peptide and would have an abnormal test result. Plasma insulin is not recommended as it does not add any additional useful information.

Type 2 Diabetes Screening and Treatment Guideline

Treatment
Goals
Cardiac risk reduction is the most important management issue for patients with diabetes. Table 3. Selected cardiac risk factors and goals for risk reduction Risk factor Blood pressure LDL cholesterol Hemoglobin A1c (HbA1c) Fasting blood glucose
1

Goal Lower than 140/801 mm HG Lower than 100 mg/dL 78%2 80120 mg/dL

For patients with diabetes, there are two HEDIS goalslower than 140/90 and lower than 140/80. The Group Health guideline goal was changed to align with the lower HEDIS goal. Certain patientssuch as younger patients and those with microalbuminuriamay benefit from achieving even lower blood pressure levels (e.g., lower than 130/80). In older patients with type 2 diabetes, there is evidence that pushing systolic blood pressure below 120 mm Hg offers no more cardiovascular benefit than pushing it below 140 mm Hg. (ACCORD 2010). Intensive systolic blood pressure control to below 120 may lead to a higher rate of adverse effects. Use clinical judgment to determine if a target lower than 7% is appropriate for an individual patient. It can be challenging to push a patients HbA1c levels from just above 7% to below 7%. There are potential benefits (decreased nonfatal myocardial infarction) and potential harms (hypoglycemia, weight gain, and possible increase in all-cause and cardiovascular-cause mortality) of intensive glucose therapy, especially in patients with known cardiovascular disease. For frail elderly patients, a target HbA1c of 79% is reasonable.

Lifestyle modifications and non-pharmacologic options

Diet and physical activity
There is some evidence that intensive programs of lifestyle interventions targeting patients with impaired fasting glucose reduce the incidence of type 2 diabetes. Lifestyle interventions include dietary and physical activity counseling. All patients should strive to: Make smart choices from every food group to meet their caloric needs. Get the most and best nutrition from the calories consumed. Find a balance between food intake and physical activity. Get at least 30 minutes of moderate-intensity physical activity on most days. For personalized eating plans and interactive tools to help patients plan and assess food choices, see the U.S. Department of Agricultures Choose My Plate website (http://www.choosemyplate.gov/). For patients who have been inactive, recommend slowly working up to at least 30 minutes of moderate physical activity per day. If they are unable to be active for 30 minutes at one time, suggest accumulating activity in 10- to 15-minute sessions throughout the day.

Weight management, including bariatric surgery

The risk of serious health conditionssuch as high blood pressure, heart disease, arthritis, and stroke, as well as diabetesincreases with body mass index (BMI) of 25 or higher. (BMI = weight in kilograms divided by height in meters squared [kg/m2].) Overweight is defined as a BMI of 25 to 29.9, obesity as a BMI of 30 or higher. While most overweight or obese adults can lose weight by eating a healthy diet or increasing physical activity, doing both is most effective.

Type 2 Diabetes Screening and Treatment Guideline

There is fair evidence from one RCT that surgically induced weight loss results in better blood glucose control and less need for diabetic medications than conventional diabetes therapy focused on weight loss through lifestyle changes. There is insufficient evidence on long-term effectiveness and safety (Dixon 2008). See the Group Health clinical review criteria for bariatric surgery (http://www.ghc.org/allsites/clinical/criteria/pdf/baricrit1.pdf). See the Group Health Weight Management Guideline for recommendations and further information.

Foot care
For patients at very high risk or increased risk of developing foot ulcers, recommend using a foot skin care kit (https://provider.ghc.org/open/caringForOurMembers/patientHealthEducation/conditionsDiseases/diabete s/footCare.pdf). Foot-ulcer risk definitions: Patients at very high risk are those with a previous foot ulcer, amputation, or major foot deformity (claw/hammer toes, bony prominence, or Charcot deformity). Patients at increased risk are those who are insensate to 5.07 monofilament at any site on either foot or who have bunions, excessive corns, or callus. Patients at average risk are those with none of the aforementioned complications. Encourage patients to check their feet regularly and follow a self-management care agreement. If the patient or a family member cannot perform the patients foot care, encourage the patient to find someone who can provide assistance.

Blood glucose controlpharmacologic options

Recommended pharmacologic options
See also the prescribing notes that follow Table 4. Table 4. Recommended pharmacologic options for blood glucose control Eligible population HbA1c above goal Line 1st Medication Biguanide MetforminNote HbA1c above goal on metformin 2nd Add insulin NPH insulinNote 12 units at bedtime Increase bedtime NPH by 4 units until fasting blood glucose is lower than 120 mg/dL or use treat-totarget strategy 18 mg once daily 250 mg once daily 1,000 mg twice daily or 850 mg three times a day Initial dose Therapeutic/goal dose

and/or

2nd

Add sulfonylureaNote Glimepiride 12 mg once daily at breakfast or first main meal (1 mg daily for elderly patients)

Type 2 Diabetes Screening and Treatment Guideline

Prescribing notes Metformin Metformin should be titrated as tolerated. A reasonable initial titration schedule is: 500 mg tab once daily X 7 days; 500 mg 1 tab once daily X 7 days; 500 mg 1 tab twice daily If a patient does not experience any GI side effects after 23 days, dose may be titrated to goal more quickly. If a patient develops GI side effects, reduce dose and reassess. Consider a more conservative titration schedule starting with 500 mg tab (125 mg) PO once daily; alternatively, consider prescribing the XL formulation for patients who cannot tolerate ideal dose with regular release formulation. Precautions with metformin prescribing: Avoid use of metformin in patients with known binge or excessive alcohol use. Instruct patients to avoid excessive acute or chronic alcohol use. Suspend use of metformin if a patient is to undergo a surgical procedure or to be given iodinated contrast media for a radiological procedure. Restart metformin when normal renal function is verified. Metformin should be withheld in patients with dehydration and/or prerenal azotemia. NPH insulin Check fasting blood glucose (FBG) every day and get weekly average. Target is mean FBG of 120 mg/dL. Less than 200 lb, FBG lower than 200 12 U and up by 4 U/week Less than 200 lb, FBG higher than 200 16 U and up by 8 U/ week More than 200 lb, FBG lower than 200 20 U and up by 4 U/ week More than 200 lb, FBG higher than 200 30 U and up by 10 U/ week Treat-to-target strategy: 1. Initial dose of 10 units of long-acting insulin at bedtime. 2. If FBG is higher than 130, increase bedtime insulin dose by 1 unit. 3. Continue increasing bedtime insulin dose by 1 unit at a time until FBG is in the target range. 4. If FBG is lower than 80, decrease bedtime insulin dose by 1 unit. 5. Continue decreasing bedtime insulin dose by 1 unit at a time until FBG is in the target range. If HbA1c is higher than 7.0% and BG checks before lunch, dinner, and bedtime are indicating a steady rise in BG throughout the day, the patient very likely needs daytime insulin therapy. Sulfonylurea For preferred sulfonylurea (Glimepiride), a reasonable titration schedule is: Increase to 2 mg once daily for 12 weeks; Increase by 2 mg once daily at 1- to 2-week intervals to maximum of 8 mg once daily. For alternative sulfonylurea (Glipizide), a reasonable titration schedule is: 5 mg tab twice daily X 7 days; 5 mg 1 tab twice daily X 7 days; 5 mg 2 tab twice daily X 7 days Consider prescribing the XL formulation for patients who cannot tolerate regular release formulation.

Type 2 Diabetes Screening and Treatment Guideline

U-500 insulin
Consider U-500 insulin for patients who are very insulin resistant and need more than 200 units of insulin per day. Consult with a diabetes expert before switching to U-500 insulin. Within Group Health, contact Dave McCulloch, MD, Dan Kent, PharmD, or a Diabetes Expert Team physician. See Regular Insulin U500: Considerations for Safe Use for more information.

Continuous subcutaneous insulin infusion (insulin pumps)

Some manufactures are pushing insulin pumps for patients with type 2 diabetes; however, there is insufficient evidence to recommend for or against the use of insulin pumps for managing patients with type 2 diabetes.

Options that are not recommended

The following pharmacologic options are not recommended or not on the Group Health formulary; consider consultation with a diabetes expert: DPP-4 inhibitorssitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta) GLP-1 agonistsexenatide (Byetta, Bydureon), liraglutide (Victoza) Alpha glucosidase inhibitorsacarbose (Precose), miglitol (Glyset) Meglitinidesrepaglinide (Prandin), nateglinide (Starlix) Thiazolidinedionesrosiglitazone (Avandia), pioglitazone (Actos) Sodium glucose transport 2 inhibitorsDapagliflozin Amylin hormonepramlinitide (Symlin) Insulin analoginsulin detemir (Levimir) (PA for children) There is no high-quality evidence to determine the effect on blood glucose control of any of the following: Chromium Cinnamon Vanadium

ASCVD prevention
Risk-reduction measures to consider include smoking cessation, blood pressure control, statin therapy, ACE inhibitor/angiotensin receptor blocker (ARB) therapy, and antiplatelet therapy. See the Group Health Cardiovascular Disease (ASCVD) Guideline for details.

Comorbidity treatment
Hypertension management
First-line treatment for patients with diabetes and hypertension is an ACE inhibitor or an ARB. See the Group Health Hypertension Guideline for details.

Sick-day management
Patients experiencing acute illnesses need to be extra vigilant about blood glucose monitoring and control. Within Group Health, the following information and help is available: The Pharmacy's It's Flu Season! Timely Reminders About Diabetes and Sick Day Care contains information about the Sick Day Kit, which is available to patients. The pamphlet Living Well with Type 2 Diabetes: Taking Care of Yourself When Youre Sick" (#338) can be ordered from the Group Health Resource Line (or use SmartPhrase .chronicdiseasedmtype2sickdayplan). Group Health pharmacy staff can help with selecting sugar-free cold medicines and cough syrups.

Type 2 Diabetes Screening and Treatment Guideline

Follow-up/Monitoring
Periodic monitoring of conditions and complications
Table 5. Self blood glucose monitoring (SBGM) Note that for patients with diabetes, SBGM is useful only if they are testing and using the result information to make changes to their diabetes self-management plans. Eligible population Patients on lifestyle changes and/or metformin only Recommendations These patients are at no risk for hypoglycemia.1 It is perfectly reasonable for them not to do SBGM. Changes to therapy can be made based on HbA1c values every 3 months. Specifically, some patients may find SBGM helps them to stay motivated with lifestyle changes to see the effect of particular food items or exercise on their blood glucose. These patients may develop hypoglycemia. It is advisable that they do SBGM when they feel funny to confirm whether or not their symptoms are due to hypoglycemia. If patients are using treat-to-target approaches, especially if using insulin (for example, titrating their dose of bedtime NPH insulin until they reach a fasting blood glucose target of 120 mg/dL), then testing the fasting blood glucose once a day is advisable. Once patients achieve their fasting blood glucose target, there is no need to continue testing every morning if they feel well and their HbA1c stays below their target range. However, if such patients are at their target for fasting blood glucose but their HbA1c is still above target, then testing before and two hours after their main meal may give useful information about the need for additional daytime treatment (with sulfonylurea or insulin). These patients should test 34 times daily if they are using the information to adjust how much fast-acting insulin they take before the meal. They may also want to test 2 hours after their main meal or under other circumstances where they want to know the effect of food, exercise, or stress on their blood glucose levels.

Patients on sulfonylureas and/or insulin

Patients on basal insulin and pre-meal fast-acting insulin

Several studies have shown that improvement in HbA1c is almost identical whether patients test their blood glucose or not (Poolsup 2009).

Type 2 Diabetes Screening and Treatment Guideline

Table 6. Recommended periodic monitoring of conditions and complications Condition/complication Hypertension Blood glucose control Test(s) Frequency BP taken with appropriate size cuff Every visit using optimal technique HbA1c Every 3 months until the target level is reached; thereafter, patient should be monitored every 6 months. Patients at very high risk2 should be seen every 3 months by a wound care nurse. Patients at increased risk2 and average risk2 should be screened annually. Annually Annually Patients with evidence of retinopathy should be screened annually. Grade A Patients without evidence of retinopathy should be screened every 2 years.3 Grade A At least annually

Foot ulcers

Physical exam focused on ankle reflexes, dorsalis pedis pulse, vibratory sensation, and 5.07 monofilament touch sensation performed by a provider qualified to determine the level of risk for foot ulcers Spot urine (microalbuminuria: creatinine ratio)1 Fasting LDL Dilated eye exam by a trained eye services professional or Non-dilated digital photography followed by a comprehensive exam for those who test positive Serum creatinine and Serum potassium

Microalbuminuria Hyperlipidemia Retinopathy

Electrolyte and chemistry abnormalities

1

The spot urine test (microalbuminuria/creatinine ratio) can identify patients with microalbuminuria by giving a quantitative estimate of protein loss that correlates with 24-hour urinary protein measurements. Test results are expressed in micrograms of urinary albumin per milligram of urinary creatinine (or A:C ratio). Group Health defines a positive test as more than 50 mcg/mg. Although the conventional definition of microalbuminuria is more than 30 mcg/mg, using more than 50 mcg/mg minimizes the number of false-positive results. Two positive (more than 50 mcg/mg) spot urine tests are diagnostic for microalbuminuria. See Foot care in the Lifestyle modifications and non-pharmacologic options section for foot-ulcer risk definitions. Annual screening is not recommended because the benefits of more frequent screening are marginal: For every 1,000 persons screened annually (instead of every second year), one additional case of proliferative diabetic retinopathy and one additional case of clinically significant macular edema will be detected.

Type 2 Diabetes Screening and Treatment Guideline

Medication monitoring
Table 7. Recommended monitoring for medication side effects Eligible population Patients who are being treated with metformin1
1

Test Serum creatinine

Frequency Annually if serum creatinine is 1.5 or lower or Twice a year if serum creatinine is higher than 1.5

For patients on metformin, serum creatinine should be monitored because the medication is primarily excreted by the kidney. Metformin can be prescribed if the serum creatinine is lower than 2.5 and if the eGFR is higher than 30, provided this value is not 25% worse than the previous reading. Use of concomitant medications that may affect renal function (i.e., affect tubular secretion) may also affect metformin excretion. Metformin should be withheld in patients with dehydration and/or prerenal azotemia; also hold prior to radiologic procedures (i.e., studies requiring administration of IV contrast) and prior to surgery.

Recommended comorbidity screening

Screen for depression by using the Patient Health Questionnaire (PHQ-9). Evidence suggests that patients with depression are less likely to be adherent to recommended management plans and less likely to be effective at self-management of diabetes. See the Group Health Adult Depression Guideline or Adolescent Depression Guideline for additional guidance. Patients with major depression can be treated in primary care or offered a referral to Behavioral Health Services for counseling and/or drug therapy.

Recommended immunizations
Table 8. Recommended immunizations for patients with diabetes1 Immunization Influenza Pneumococcal (PPV23) Hepatitis B1
1

Frequency Annually, as early as possible when vaccine becomes available Once between 19 and 64 years Booster after 65 years (5-year minimal interval) Three-dose series for 19 to 59 years 60 years and older, depending on risk

See the CDCs Recommended Adult Immunization Schedule for more detailed information (http://www.cdc.gov/vaccines/recs/schedules/downloads/adult/adult-schedule.pdf). Results from observational studies suggest that patients with diabetes are at higher risk for hepatitis B compared to patients without diabetes (CDC 2011).

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Evidence Summary
Group Health developed the Type 2 Diabetes Screening and Treatment Guideline using an evidencebased process, including systematic literature search, critical appraisal, and evidence synthesis.

Prevention
Pharmacologic treatment to delay diabetes
Metformin Results from a recent meta-analysis of 31 randomized controlled trials (RCTs) illustrated that treatment with metformin reduced the absolute risk of diabetes by 6% during a mean duration of 1.8 years. Subjects receiving metformin also experienced modest improvements in BMI, LDLcholesterol, and HDL-cholesterol compared to subjects receiving either placebo or no intervention (Salpeter 2008). The study analyzed metabolic risk factors and not clinical outcomes, leaving unanswered the question of whether delaying diabetes improves clinical outcomes. Valsartan There is fair evidence from an RCT that the use of valsartan, an angiotensin-receptor blocker (ARB), along with lifestyle modification, led to a 14% relative reduction in the incidence of diabetes compared to lifestyle modification alone (NAVIGATOR 2010). However, there is not evidence that valsartan improves clinical outcomes.

Screening recommendations and tests

Screening hypertensive patients for diabetes
There is no direct evidence from RCTs that systematic screening for diabetes results in better health outcomes than identifying diabetes clinically. The recommendation to screen patients with known hypertension is based on indirect evidence. In particular, the recommendation is based on evidence from RCTs that when patients have diabetes as well as hypertension, additional lowering of blood pressure results in a greater reduction in cardiovascular events and cardiovascular mortality (USPSTF 2008).

Screening pregnant women for gestational diabetes

There is evidence from one RCT that a comprehensive program of treating gestational diabetes (dietary advice, self-monitoring of glucose level, and insulin if needed) reduced infant complications compared to usual care. The rate of infant complications (composite measure) was 1% in the intervention group and 4% in the control group, NNT = 34. There was no significant difference in the rate of cesarean section. Although this was not a screening trial, its findings suggest that screening and treating pregnant women is beneficial (Crowther 2005).

Diagnosis
Use of HbA1c to diagnose diabetes
A cross-sectional study compared HbA1c of 6.5% or higher and fasting plasma glucose (FPG) of 126 mg/dL or higher for the identification of undiagnosed diabetes among National Health and Nutrition Examination Survey (NHANES) participants. When using HbA1c of 6.5% or higher and FPG of 126 mg/dL or higher as the cut-points for diabetes, results showed that there is moderate agreement between the two tests for the diagnosis of diabetes. Diabetes classification was consistent for the majority of the subjects, with 95.9% being classified as positive by both tests and 1.8% being classified as negative by both tests. Only 0.5% of subjects were classified as positive by one test and negative by the other (Carson 2010).

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Treatment
Goals
Blood pressure There is good evidence from one RCT that intensive lowering of systolic blood pressure below 120 mm Hg did not reduce the combined risk of fatal or nonfatal cardiovascular events (ACCORD 2010, NEJM p. 1575). Blood glucose control Three meta-analyses compared the effects of tight blood glucose control versus standard therapy (Turnbull 2009, Kelly 2009, Ray 2009). Tight blood glucose control appears to reduce the risk of nonfatal myocardial infarction; however, there is an increased risk of hypoglycemia and weight gain. Additionally, the ACCORD trial suggests that all-cause mortality is increased with intensive treatment compared to standard treatment (ACCORD, NEJM 2008). Results from an exploratory post hoc analysis from the ACCORD trial suggest that this trend may be even more striking among patients with baseline HbA1c levels higher than 8.5% and those with neuropathy (CallesEscandon 2010). There is evidence from two major RCTs, the Diabetes Control and Complications Trial (DCCT) for type 1 diabetes and the UK Prospective Diabetes Study for type 2 diabetes (UKPDS), that blood glucose control delays the onset and slows the progression of diabetic retinopathy (DCCT 1993, UKPDS Lancet 1998). Both studies randomized patients with diabetes to receive intensive blood glucose control or conventional treatment. The DCCT found that among patients with no retinopathy at study entry, intensive blood glucose control therapy reduced the risk of progression of retinopathydefined as a sustained change on retinal photographyby 3.5% per year (NNT = 29). However, the reduction in the risk of retinopathy progression associated with a lower HbA1c was accompanied by an increased risk of hypoglycemia. For patients with mild retinopathy at the beginning of the DCCT, intensive therapy reduced the risk of laser treatment of retinopathy by 1.4% per year (NNT = 71). Target HbA1c There were no randomized controlled trials that addressed the appropriate HbA1c levels for patients with type 2 diabetes. Evidence pertaining to target HbA1c levels comes from a retrospective cohort study that was designed to address the association between all-cause mortality and HbA1c levels. Results from this study showed that for those in cohort 1 (metformin plus sulfonylurea), subjects with HbA1c levels lower than 6.72% or higher than 9.85% were at increased risk for all-cause mortality. For those in cohort 2 (insulin regimen), subjects with HbA1c levels lower than 7.4% or higher than 9.12% were at increased risk for all-cause mortality (Currie 2010).

Lifestyle modifications and non-pharmacologic options

Diet
According to the UKPDS, with dietary advice alone 16% of patients with type 2 diabetes will have fasting plasma glucose levels lower than 108 mg/dL after 3 months, and 8.5% will still be controlled by diet after 15 months (UKPDS 1990). Factors associated with long-term dietary success: Providing meal plans and grocery lists (Wing 1996). Recording foods eaten (Guare 1989). Incorporating regular exercise into the program (Wood 1991).

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Exercise
A meta-analysis of 14 RCTs on exercise in patients with type 2 diabetes showed an improvement in HbA1c of 0.6 points (95% CI = 0.3 to 0.9 points). The duration of exercise training ranged from 8 weeks to 12 months (Thomas 2006).

Bariatric surgery
There is fair evidence from one RCT that surgically induced weight loss results in better blood glucose control and less need for diabetic medications than conventional diabetes therapy focused on weight loss through lifestyle changes. There is insufficient evidence on long-term effectiveness and safety (Dixon 2008).

Blood glucose controlpharmacologic options

Metformin A study found that metformin improved blood glucose control and lipid concentrations in patients with type 2 whose diabetes was poorly controlled by diet and glyburide. The addition of up to 2,500 mg metformin per day resulted in a 20% absolute increase in the proportion of patients with fasting plasma glucose levels of lower than 140 mg/dL (DeFronzo 1995). Sulfonylureas A subgroup analysis of a prospective cohort study that included 459 patients assessed the impact of different classes of sulfonylureas on in-hospital mortality and rhythm or ischemic complications (a composite of reinfarction, arrhythmias, and stroke) in diabetic patients admitted for an acute myocardial infarction. Findings from this study suggest that when the newer sulfonylureas (glimepiride/glicalzide) were compared to glibenclamide, an older sulfonylurea, patients who were prescribed the newer agents had significantly lower mortality rates and rhythm or ischemic complications (Zeller 2010). Rapidly acting insulin analogs versus regular insulin A Cochrane Library meta-analysis of RCTs published through September 2005 found a statistically significant reduction of HbA1c with short-acting insulin analogs compared to regular human insulin for patients with type 1 diabetes. However, the difference in HbA1c was small and may not be clinically significant (weighted mean difference = 0.1% [-0.2% to 0.1%]). There were no statistically significant differences in HbA1c for patients with type 2 diabetes, or in hypoglycemic episodes for type 1 or type 2 diabetes (Siebenhofer 2006). The meta-analysis was limited by the overall low quality and short duration of the RCTs. Insulin detemir A recent meta-analysis of RCTs compared insulin detemir to NPH insulin in people with type 2 diabetes. Results indicated that patients taking NPH insulin had lower HbA1c levels than those taking insulin detemir; however, patients taking detemir were less likely to experience nocturnal hypoglycemia. There was no data available regarding the long-term safety of insulin detemir (Singh 2009).

Follow-up/monitoring
Microalbuminuria
There is no direct evidence from randomized or non-randomized controlled screening trials that microalbuminuria screening improves health outcomes. The recommendation for microalbuminuria screening is based on indirect evidence that the natural history of diabetic renal disease is well known, that screening can identify early disease, and that treatment of patients with microalbuminuria has been shown to improve health outcomes. According to data from the UK Prospective Diabetes Study (UKPDS), for patients newly diagnosed with type 2 diabetes, the annual rate of progression from no nephropathy to microalbuminuria is 2% and from microalbuminuria to macroalbuminuria is 2.8% (Adler 2003).

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Neuropathy
There is fair evidence that diabetic foot screening prevents adverse outcomes. One RCT reported outcomes in patients with diabetes assigned to a foot screening and protection program versus outcomes in those receiving usual care. At the end of 2 years, there were significantly fewer amputations in the footscreening group, but no significant difference in the incidence of ulcers. The number needed to screen (NNS) to prevent one amputation = 63 and to prevent one major amputation = 91 (McCabe 1998). No RCTs attempting to replicate these findings were identified.

Retinopathy
There is no direct evidence from randomized or non-randomized controlled screening trials that retinal screening improves health outcomes. The recommendation for retinal screening is based on indirect evidence: namely, that the natural history of diabetic retinal disease is well known, that screening can identify early disease, and that treatments such as blood glucose control and laser therapy have been shown to improve health outcomes. Two cohort studies investigated the optimum screening interval by grade of retinopathy. Both studies found that for patients at low risk for retinopathy, a 2-year screening interval was not associated with increased risk (Younis 2003, Misra 2009). Non-mydriatic digital stereoscopic retinal imaging A recent meta-analysis that included 20 observational studies and 4,059 patients examined how mydriasis influenced the accuracy of screening for diabetic retinopathy. Findings from this analysis suggest that mydriatic status alone did not significantly influence the sensitivity or specificity to detect any diabetic retinopathy (Bragge 2011). Results from an observational study that examined the sensitivity and specificity of non-mydriatic digital stereoscopic retinal imaging (NMDSRI) compared to dilated retinal examination performed by an ophthalmologist or an optometrist found that NMDSRI has a sensitivity of 98% and a specificity of 100% for retinopathy within one grade of that indicated by dilated retinal exam (Ahmed 2006). These findings were supported by the results of several other observational studies (Aptel 2008, Boucher 2003, Lin 2002, Vujosevic 2009).

Self-monitoring of blood glucose

A recent meta-analysis indicated that for patients with established type 2 diabetes not using insulin, SMBG significantly reduced HbA1c levels compared with non-SMBG; however, this is only of modest clinical significance. In a subgroup analysis, SMBG with the use of its results to modify treatment regimens significantly decreased HbA1c compared to non-SMBG (Poolsup 2009). Only one RCT looked at the effect of SMBG in newly diagnosed type 2 diabetic patients. This study found that SMBG had no effect on blood glucose control, but was associated with a 6% higher score on a depression index (OKane 2008).

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References
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-2559. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-1585. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR; UKPDS Group. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int. 2003;63(1):225-232. Ahmed J, Ward TP, Bursell SE, Aiello LM, Cavallerano JD, Vigersky RA. The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy. Diabetes Care. 2006;29(10):22052209. Aptel F, Denis P, Rouberol F, Thivolet C. Screening of diabetic retinopathy: effect of field number and mydriasis on sensitivity and specificity of digital fundus photography. Diabetes Metab. 2008;34(3):290-293. Boucher MC, Gresset JA, Angioi K, Olivier S. Effectiveness and safety of screening for diabetic retinopathy with two nonmydriatic digital images compared with the seven standard stereoscopic photographic fields. Can J Ophthalmol. 2003;38(7):557-568. Bragge P, Gruen RL, Chau M, Forbes A, Taylor HR. Screening for presence or absence of diabetic retinopathy: a meta-analysis. Arch Ophthalmol. 2011;129(4):435-444. Calles-Escandon J, Lovato LC, Simons-Morton DG, et al. Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care. 2010;33(4):721-727. Carson AP, Reynolds K, Fonseca VA, Muntner P. Comparison of A1c and fasting glucose criteria to diagnose diabetes among U.S. adults. Diabetes Care. 2010(1);33:95-97. Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011;60(50):1709-1711. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352(24):2477-2486. Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective study. Lancet. 2010;375(9713):481-489. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus.The Multicenter metformin Study Group. N Engl J Med. 1995;333(9):541-549. The Diabetes Control and Complications Trial Research Group (DCCT). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986. Dixon JB, OBrien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299(3):316-323. Guare JC, Wing RR, Marcus MD, et al. Analysis of changes in eating behavior and weight loss in type II diabetic patients: which behaviors to change. Diabetes Care. 1989;12(7):500-503. Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151(6):394-403. Lin DY, Blumenkranz MS, Brothers RJ, Grosvenor DM. The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: a comparison with ophthalmoscopy and standardized mydriatic color photography. Am J Ophthalmol. 2002;134(2):204213. Type 2 Diabetes Screening and Treatment Guideline 15

McCabe CJ, Stevenson RC, Dolan AM. Evaluation of a diabetic foot screening and protection programme. Diabet Med. 1998;15(1):80-84. Misra A, Bachmann O, Greenwood RH, et al. Trends in yield and effects of screening intervals during 17 years of a large UK community-based diabetic retinopathy screening programme. Diabet Med. 2009;26(10):1040-1047. NAVIGATOR Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477-1490. OKane MJ, Bunting B, Copeland M, Coates VE; EMSON study group. Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled trial. BMJ. 2008;336(7654):1174-1177. Poolsup N, Suksomboon N, Rattanasookchit S. Meta-analysis of the benefits of self-monitoring of blood glucose on glycemic control in type 2 diabetes patients: an update. Diabetes Technol Ther. 2009;11(12):775-784. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373(9677):1765-1772. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med. 2008;121(2):149-157. Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. Cochrane Database Syst Rev. 2006;(2):CD003287. Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. CMAJ. 2009;180(4):385-397. Thomas DE, Elliott EJ, Naughton GA. Exercise for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2006;(3):CD002968. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009;52(11):2288-2298. UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 7: Response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients. Metabolism. 1990;39(9):905-912. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854. Vujosevic S, Benetti E, Massignan F, et al. Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs 7 standard early treatment diabetic retinopathy study fields. Am J Ophthalmol. 2009;148(1):111-118. Wing RR, Jeffery RW, Burton LR, Thorson C, Nissinoff KS, Baxter JE. Food provision vs. structured meal plans in the behavioral treatment of obesity. Int J Obes Relat Metab Disord. 1996;20(1):56-62. Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N Engl J Med. 1991;325(7):461-466. Younis N, Broadbent D, Vora JP, Harding SP. Incidence of sight-threatening retinopathy in patients with type 2 diabetes in the Liverpool Diabetes Eye Study: a cohort study. Lancet. 2003;361(9353):195-200. Zeller M, Danchin N, Simon D, et al; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction investigators. Impact of type of preadmission sulfonylureas on mortality and cardiovascular outcomes in diabetic patients with acute myocardial infarction. J Clin Endocrinol Metab. 2010;95(11):4993-5002.

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Guideline Development Process and Team

Development process Group Health developed the Type 2 Diabetes Screening and Treatment Guideline using an evidencebased process, including systematic literature search, critical appraisal, and evidence synthesis. This edition of the guideline was approved for publication by the Guideline Oversight Group in May 2012. Team The Type 2 Diabetes Screening and Treatment Guideline development team included representatives from the following specialties: family medicine, nursing, and pharmacy. Clinician lead: David K. McCulloch, MD, Medical Director, Clinical Improvement, mcculloch.d@ghc.org Guideline coordinator: Avra Cohen, MN, Clinical Improvement & Prevention, cohen.al@ghc.org Chris Amante, Clinical Publications, Clinical Improvement & Prevention Kerri Ashling, MD, Family Medicine Meredith Cotton, RN, Diabetes Education Team Dora Davis, RN, Diabetes Education Team Rebecca Doheny, MPH, Epidemiologist, Clinical Improvement & Prevention John Kaschko, MD, Family Medicine Dan Kent, RPh, Pharmacy Administration Mamatha Palanati, MD, Family Medicine, Diabetes Education Team Kathryn Ramos, Patient Health Education Resources, Clinical Improvement & Prevention Sandy Randles, RN, Diabetes Education Team Tim Scholes, MD, Family Medicine, Diabetes Education Team Rosemary Schreoter, MD, Family Medicine, Diabetes Education Team Alan Searle, MD, Family Medicine, Diabetes Education Team Wende Wood, MD, Family Medicine, Diabetes Education Team

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Appendix 1. Recommendation Grade Labels

This labeling system is adapted from the U.S. Preventive Services Task Force (USPSTF). The label is based on the degree to which the evidence supports the specific clinical recommendation as written by the Group Health guideline team. In this system, certainty refers to the likelihood that the guideline teams assessment of net benefit (i.e., the benefit minus harm of the service as implemented in a general primary care population) is correct, based on the nature of the overall evidence available. While the grades are useful tools in assessing recommendations, they are not meant to replace the clinical judgment of the individual provider or to establish a standard of care.

About the labeling system

Recommendation grade definitions

Label Grade A Grade B Grade C Definition The service is recommended. There is high certainty that the net benefit (i.e., benefits minus harms) is substantial. The service is recommended. There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. The recommendation is against routinely providing the service. There may be considerations that support providing the service to an individual patient. There is at least moderate certainty that the net benefit is small. The recommendation is against providing the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. The current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms. Expert opinion refers to the collective opinion of the Group Health guideline team. The language of the recommendation is at the team's discretion. The evidence is assumed to be insufficient unless otherwise stated. In the rare case there is fair or good evidence, the evidence does not support the expert opinion recommendation put forth by the team.

Grade D I statement

Expert opinion

Levels of certainty regarding net benefit

Level of certainty High Description The available evidence usually includes consistent results from well-designed, wellconducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies. The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by such factors as: The number, size, or quality of individual studies Inconsistency of findings across individual studies Limited generalizability of findings to routine primary care practice Lack of coherence in the chain of evidence As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion. The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of: The limited number or size of studies Important flaws in study design or methods Inconsistency of findings across individual studies Gaps in the chain of evidence Findings that are not generalizable to routine primary care practice A lack of information on important health outcomes More information may allow an estimation of effects on health outcomes.

Moderate

Low

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